Tisagenlecleucel Associated With Improved Response Rates, Reduced Risk of Death vs Historical Treatments for DLBCL

Third-line or later treatment with tisagenlecleucel is associated with significantly higher response rates and significantly lower risk of death compared with historical control treatments for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a recent study.

The study, published in Blood Advances, indirectly compared overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel using data from the JULIET study vs historical treatments assessed in the CORAL study.

“No head-to-head trials have compared the efficacy of tisagenlecleucel vs historical treatments for adults with relapsed or refractory [DLBCL],” wrote lead author Richard Maziarz, MD, Oregon Health and Science University Hospital, Portland, and coauthors.

There were 2 separate comparisons: the full analysis set (FAS) of the JULIET study vs the CORAL follow-up FAS and the JULIET study intention-to-treat (ITT) population vs the CORAL follow-up ITT population.  

In the JULIET trial, 167 patients constituted the ITT population, 115 of whom were infused with tisagenlecleucel; these made up the JULIET FAS. The overall response rate (ORR) among patients receiving tisagenlecleucel was 52%, with a complete response (CR) rate of 41%.

In the CORAL study, 477 participants were enrolled from July 2003 to June 2008 and treated with second-line therapy (1 of 2 chemotherapy regimens followed by autologous hematopoietic cell transplantation when feasible); 170 made up the FAS.

To compare OS and ORR, Dr Maziarz and colleagues used propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW), adjusting for baseline confounding factors.

Tisagenlecleucel was associated with a lower hazard of death among both the FAS (adjusted hazard ratio [aHR], 0.44; 95% confidence interval [CI], 0.32to 0.59] for both FSW and SMRW) and ITT populations (FSW: aHR, 0.60; 95% CI, 0.44 to 0.77; SMRW: aHR, 0.57; 95% CI, 0.44 to 0.73; all, P <.001). In the FAS comparison, median OS was 12.48 months in JULIET vs 4.34 to 4.4 months in CORAL. For the ITT population, the median OS was 8.25 months in JULIET vs 4.04 to 4.86 months in CORAL.

In addition, tisagenlecleucel was associated with a significantly higher ORR compared with historical treatments in the FAS (adjusted response rate difference, 36%; 95% CI, 22% to 0.48%] for both FSW and SMRW; P < .001) and in the ITT populations after SMRW adjustment (adjusted response rate difference, 11%; 95% CI, 0% to 22%]; P = .043).

“This analysis supports that improved response and OS are achieved in patients with [relapsed/refractory] DLBCL treated with tisagenlecleucel compared with those treated with alternative historical treatments,” concluded Dr Maziarz and colleagues.

Source:

Maziarz R, Zhang J, Yang H, et al. Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2022;6(8):2536-2547. doi:10.1182/bloodadvances.2021006280.